Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal hemodynamics, plasma renin activity (PRA), plasma aldosterone (PA) and sodium excretion were studied in essential hypertension. PAH clearance (CPAH) and glomerular filtration rate (GFR) were normal or increased in early hypertension and depressed at later stages, especially in malignant cases. The PAH extraction ratio was depressed only in patients with low CPAH values. CPAH did not correlate inversely with blood pressure in benign hypertension. Later reexamination of untreated patients revealed a decrease in CPAH, but no further increase in blood pressure. Antihypertensive treatment prevented the decrease in CPAH. Patients with essential hypertension showed no abnormality in basal sodium excretion, plasma aldosterone, plasma renin activity and the sodium:aldosterone relationship. Basal sodium clearance did not correlate with GFR and the fractional sodium excretion was not pressure-dependent. When clearance determinations and measurements of PA and PRA were performed simultaneously under standardized conditions, PA and PRA were correlated inversely with CPAH and GFR. There was no relationship between PA or PRA and the blood pressure. Unless a defective release of renal prostaglandins and/or kinins could be shown to be responsible for the increase in systemic blood pressure, there is no evidence for a primary renal disturbance in essential hypertension.
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PMID:Relationships between sodium clearance, plasma renin activity, plasma aldosterone, renal hemodynamics and blood pressure in essential hypertension. 700 Apr 63

Labetalol, a blocker of alpha- and beta-adrenoreceptors, was tried on 45 patients with severe (29 cases) or mild to moderate (16 cases) hypertension. After an initial period of dosage adjustment and a 2 months treatment in effective doses, there was a significant fall in supine blood pressure from mean values of 207/132 to 170/106 mmHg. In 23 patients hypertension was controlled by labetalol alone in doses of 400 and 1800 mg per day. True failures were rare (16%). Digestive disorders and postural hypotension were the most frequently encountered side-effects; they obliged to discontinue treatment in 4 cases, but were compatible with it in 11 cases. In 22 patients the fall in BP was accompanied by a significant (p less than 0,001) decrease in plasma renin activity from 123 to 44 ng/l/min supine and from 144 to 83 ng/l/min standing. Studies of the renal function showed no changes during oral therapy. Following intravenous injection of 50 mg labetalol to 20 subjects, inulin and PAH clearances remained unaltered, and there was a significant, though transient (1 hour), decrease in chloride, sodium and phosphorus excretion. Effective in lowering blood pressure be used and well tolerated by the kidneys, labetalol can safely be used for the treatment of severe hypertension with organic renal involvement.
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PMID:[Effects of labetalol, a new alpha- and beta-adrenoreceptor blocking drug, on arterial pressure, renal function and renin activity (author's transl)]. 700 20

1. Issuing from the clinical method of proceeding in side-separated diagnosis of the renal function under theoretical aspect a survey orientation for the renal global function is tried. 2. The method orientation is done according to semiquantitative and quantitative valuation. The isotope and contrast remedy urography, the functional tests after Howard, Rapoport and Stamey, the conventional side-separated estimation of the clearance, the isotope sequence scintigraphy as well as the diagnostics of the renal and intrarenal haemodynamics (renin determination, measuring of the renal plasma flow by means of PAH and other indicators [133-xenon-wash-our-technique]). 3. Finally a valuation of the method concerning the side-separated diagnostics of the renal elimination function as well as of the stenosis of the renal arteries is done taking into consideration the performability of the investigation methods in the clinic.
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PMID:[Physiological-pathophysiological evaluation of possibilities and limits of unilateral renal function tests]. 701 Aug 32

CsA associated hyperkalaemia was investigated in 24 renal transplant recipients 6 months after transplantation. 51Cr-EDTA-, PAH-, lithium and sodium clearances, 24 h urinary creatinine and potassium excretions, plasma renin activity and aldosterone concentrations were measured. Transtubular potassium concentration gradient (TTKG) was calculated. An ACTH test was performed to document adrenal function. Eleven patients had hyperkalaemia. The TTKGs were low normal or reduced in both normo- and hyperkalaemic patients implying inhibition of K+ secretion. The hyperkalaemic patients received more CsA (mean dose 21.3 vs. 9.7 mg kg-1d-1, P = 0.01), and had lower lithium clearances (mean 9.9 vs. 17.0 mL min-1 1.73 m-2, P < 0.05). Adrenal function had no clear effect. Serum potassium concentration correlated with CsA dose (r = 0.773, P < 0.001) and inversely with lithium clearance (r = -0.568, P < 0.01) suggesting that CsA induced decrease in distal tubular flow rate reduced K+ excretion. Hyperkalaemia was not fully explained by renal mechanisms.
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PMID:Renal and adrenal mechanisms in cyclosporine-induced hyperkalaemia after renal transplantation. 749 41

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. 807 55

To determine the renal functional reserve in renal transplant recipients, we measured the glomerular filtration rate by inulin clearance and the renal plasma flow by PAH clearance before and during an amino acid infusion (Totamine, 6 to 8 mg/kg/min for 90 to 120 min) in 18 transplanted patients with stable renal function. To test the role of the renin-angiotensin system on the renal functional reserve, we performed a crossover placebo-controlled randomized trial of acute blockade of the renin-angiotensin system by injection of perindoprilat (2 mg i.v.), an inhibitor of angiotensin converting enzyme before amino acid infusion, each patient being studied twice at seven day intervals. Amino acid infusion induced a time-dependent increase in the glomerular filtration rate (P = 0.04), whether or not the renin-angiotensin system was blocked. Maximal increases were from 49.1 +/- 4.1 to 58.9 +/- 5.4, mean +/- SE (18.5%), in control conditions and from 52.4 +/- 5.6 to 62.1 +/- 5.5 ml/min/1.73 m2 (19.7%) after perindoprilat. The increase in glomerular filtration rate was less pronounced in patients taking cyclosporin A than in patients treated with steroid and azathioprine. Amino acid infusion also induced a significant and time-dependent increase (15.2 to 20.2%) in the renal plasma flow (P < 0.01) whether or not perindoprilat had been given. Furthermore, perindoprilat alone increased renal plasma flow by 13.6%, and this effect seemed additive with that of amino acids. Perindoprilat injection decreased filtration fraction (from 0.20 +/- 0.01 to 0.19 +/- 0.01). This parameter returned to basal values after amino acid infusion (0.20 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients. 835 58

Ascites becomes refractory to medical treatment in nearly 10% of cirrhotic patients, who then require repeated large-volume paracentesis. In this prospective study we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 30 patients with refractory ascites. TIPS was successful in all and resulted in a 54% reduction in portacaval gradient (from 22.8 +/- 0.8 to 10.4 +/- 0.6 mm Hg). Ascites became easily controlled with diuretics in 26 patients following TIPS. Ascites recurrence associated with shunt stenosis was observed during follow-up in eight patients; revision could be undertaken in five of them and resulted in good control of ascites. In responders, a marked decrease in plasma aldosterone and renin activity, a reduction in serum creatinine, and a rise in urinary sodium excretion were observed. Creatinine and inulin clearances improved significantly; PAH clearance remained unchanged. However, new-onset or worsening hepatic encephalopathy was seen in 14 patients. Severe disabling chronic encephalopathy occurred in five patients; it could be reversed successfully by balloon occlusion of the shunt in three. The cumulative survival rate was 41 and 34% at 1 and 2 years, respectively. In summary, TIPS can control refractory ascites in a majority of patients but is associated with a high rate of chronic disabling HE. In addition, the survival rate is poor. Randomized trials are needed to evaluate the exact role of TIPS in the management of refractory ascites. It is unlikely to improve survival but can ameliorate quality of life in nontransplant candidates and be useful as a bridge to transplantation, in particular, to improve denutrition associated with longstanding tense ascites.
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PMID:Treatment of refractory ascites using transjugular intrahepatic portosystemic shunt (TIPS): a caution. 900 33

The vascular effects of angiotensin converting enzyme inhibitors are mediated by the inhibition of the dual action of angiotensin converting enzyme (ACE): production of angiotensin II and degradation of bradykinin. The deleterious effect of converting enzyme inhibitors (CEI) on neonatal renal function have been ascribed to the elevated activity of the renin-angiotensin system. In order to clarify the role of bradykinin in the CEI-induced renal dysfunction of the newborn, the effect of perindoprilat was investigated in anesthetized newborn rabbits with intact or inhibited bradykinin B2 receptors. Inulin and PAH clearances were used as indices of GFR and renal plasma flow, respectively. Perindoprilat (20 microg/kg i.v.) caused marked systemic and renal vasodilation, reflected by a fall in blood pressure and renal vascular resistance. GFR decreased, while urine flow rate did not change. Prior inhibition of the B2 receptors by Hoe 140 (300 microg/kg s.c.) did not prevent any of the hemodynamic changes caused by perindoprilat, indicating that bradykinin accumulation does not contribute to the CEI-induced neonatal renal effects. A control group receiving only Hoe 140 revealed that BK maintains postglomerular vasodilation via B2 receptors in basal conditions. Thus, the absence of functional B2 receptors in the newborn was not responsible for the failure of Hoe 140 to prevent the perindoprilat-induced changes. Species- and/or age-related differences in the kinin-metabolism could explain these results, suggesting that in the newborn rabbit other kininases than ACE are mainly responsible for the degradation of bradykinin.
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PMID:Role of bradykinin in the neonatal renal effects of angiotensin converting enzyme inhibition. 945 May 2

Nebivolol (CAS 99200-09-6) is a novel beta 1-selective adrenoceptor antagonist which possesses vasodilating properties and lowers systemic vascular resistance in dogs and humans, presumably by a nitric oxide-related mechanism. In the present study, clearance techniques were applied to anaesthetized male Sprague Dawley rats, and the effects of nebivolol on renal hemodynamics (glomerular filtration rate and renal plasma flow), on urinary excretion of sodium, chloride and potassium, on renal NO-excretion, and on plasma renin activity were studied. Nebivolol doses ranging from 0.1 to 2 mg/kg i.v. were tested. The results revealed that nebivolol dose-dependently increased glomerular filtration rate, urine flow and urinary excretion of sodium and chloride. Potassium excretion was only inconsistently increased and showed no dose dependency. At a dose of 1 mg/kg, the drug also significantly increased renal plasma flow measured as 3H-PAH (p-aminohippurate) clearance. The effect of nebivolol on the glomerular filtration rate could be abolished by L-NMMA (N6-monomethyl-L-arginine) (1 mg/kg), a non-selective inhibitor of NO-synthase and by iminoethyllysine (1 mg/kg), a relatively selective inhibitor of the inducible NO-synthase, but not by 7-nitroindazole (1 mg/kg), a relatively selective inhibitor of the neuronal NO-synthase isoform. The saluretic effect of nebivolol was diminished by all of the three NO-synthase inhibitors, but could not be completely reversed. At a dose of 2 mg/kg, nebivolol increased renal NO-excretion by 70.7%. This effect could be completely abolished by L-NMMA (1 mg/kg). Plasma renin activity was lowered by nebivolol (2 mg/kg) from 14.6 +/- 1.49 to 6.5 +/- 1.66 ng angiotensin I/ml/h (p < 0.01). The results demonstrate that, in anaesthetized rats, nebivolol exerts significant renal vasodilating effects and increases urinary excretion of fluid and solutes. The actions of nebivolol on renal hemodynamics are assumed to be mediated by a stimulation of the NO-synthase, probably the inducible isoform. Since none of the NO-synthase inhibitors could completely abolish the saluretic effect of nebivolol, an additional mechanism, not related to NO, may be involved in the tubular action of this drug.
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PMID:Effect of nebivolol, a novel beta 1-selective adrenoceptor antagonist with vasodilating properties, on kidney function. 1114 63

p38 mitogen-activated protein kinase (p38) has been implicated in mediating vascular smooth muscle and mesangial cell contraction in response to several vasoactive factors, including angiotensin II. Early stages of diabetic nephropathy are associated with renal hemodynamic changes that are, at least in part, attributable to the dysbalance of vasoactive factors that control afferent and efferent arteriolar tone resulting in increased glomerular capillary pressure. Vascular and renal p38 have been found to be activated in diabetes. Therefore, p38 may be involved in the control of systemic and renal hemodynamics in diabetes. To address this issue, mean arterial blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), metabolic parameters, and plasma renin concentrations (PRC) were determined in streptozotocin-diabetic rats (DM), and in age-matched non-diabetic controls (C), administered with the p38 inhibitor SB 239063 (SB, 50 mg/bwt, p.o.) or with vehicle. Furthermore, renal vascular responses to p38 inhibition (SB 202190, 25 microM) before and after stimulation with the endothelium-dependent vasodilator acetylcholine (ACh) were studied in vitro in tertiary branches of the renal artery from separate groups of DM and C rats, using a fixed support and a force transducer in a myograph system. SB treatment was associated with marked reductions in MAP and GFR in both C and DM rats, whereas RPF remained unchanged, as compared with vehicle-treated animals. Observed differences in MAP and renal hemodynamics were not associated with changes in urinary sodium excretion or PRC. Incubation of KCl-contracted renal arteries from both C and DM rats with the p38 inhibitor resulted in progressive and significant vasorelaxation. Also, vessels from control and diabetic rats treated with the p38 inhibitor exhibited enhancement of ACh-induced vasorelaxation. These data indicate the role of p38 in the control of systemic and renal hemodynamics both in normal and in diabetic rats. The observed effects of p38 inhibition could be mediated at least in part by enhancement of endothelium-dependent vasodilation.
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PMID:Effects of p38 mitogen-activated protein kinase inhibition on blood pressure, renal hemodynamics, and renal vascular reactivity in normal and diabetic rats. 1802 96


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